Sleeping Disorders
Last Updated: November 7, 2002
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Synonyms and related keywords: disorders of initiating and maintaining sleep (DIMS), dyssomnias, insomnia, parasomnias, sleep-wake cycle disturbances, sleep apnea, REM sleep, non-REM sleep
AUTHOR INFORMATION Section 1 of 10
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Author: Curley L Bonds, MD, Clinical Assistant Professor, Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles
Curley L Bonds, MD, is a member of the following medical societies: American Medical Association, and American Psychiatric Association
Editor(s): Denis F Darko, MD, Vice President and Medical Director, California Clinical Trials Medical Group, Inc; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine; Iqbal Ahmed, MD, Program Director, General and Geriatric Psychiatry Residency Programs, Vice Chair for Education, Professor, Department of Psychiatry, John A Burns School of Medicine, University of Hawaii; Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry, Assistant Professor, Department of Medicine, Froedtert Hospital, Medical College of Wisconsin; and Stephen Soreff, MD, Director of Quality Improvement, President of Education Initiatives, HMA Behavioral Health, Inc
INTRODUCTION Section 2 of 10
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Background:
Sleep disorders are among the most common clinical problems encountered in medicine, including in psychiatry. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) divides all sleep disorders into 3 general groups: primary, secondary to a mental disorder, and others, namely those related to a general medical condition or substance abuse.
Primary sleep disorders are presumed to result from an endogenous disturbance in sleep-wake generating or timing mechanisms, often complicated by behavioral conditioning. These disorders are further subdivided into parasomnias and dyssomnias. Parasomnias are characterized by abnormal behavioral or physiological events in association with sleep, sleep stages, or sleep-wake transitions, rather than increased or decreased sleep. Parasomnias include nightmare disorder, sleep terror disorder, and sleepwalking disorder. Dyssomnias are characterized by abnormalities in the amount, quality, or timing of sleep. These include primary insomnia and hypersomnia, narcolepsy, breathing-related sleep disorder (ie, sleep apnea), and circadian rhythm sleep disorder. This article focuses primarily on insomnia, rather than the numerous other sleep disorders.
Primary insomnia is the general term for difficulty in initiating or maintaining sleep. Because sleep requirements vary from individual to individual, insomnia is considered clinically significant when a patient perceives the loss of sleep as a problem. Insomnia may be characterized further as acute (transient) or chronic.
Pathophysiology:
Rapid eye movement and nonrapid eye movement
Sleep is divided into 2 categories, rapid eye movement (REM) and nonrapid eye movement (NREM). Each of these sleep states is associated with distinct central nervous system activity.
NREM sleep is further divided into 4 progressive categories, termed stages 1-4 sleep. The arousal threshold rises with each stage of sleep, with stage 4 (delta) being the sleep state from which a person is least able to be aroused, characterized by high-amplitude slow waves.
REM sleep is characterized by muscle atonia, episodic REMs, and low-amplitude fast waves on electroencephalogram (EEG) readings. Dreaming occurs mainly during REM sleep.
Disturbances in the pattern and periodicity of REM and NREM sleep often are found when people complain of sleep disorders.
Sleep-wake cycles
Sleep-wake cycles are governed by a complex group of biological processes that serve as internal clocks.
The supra chiasmatic nucleus, located in the hypothalamus, is thought to be the body’s anatomic timekeeper, responsible for the release of melatonin on a 25-hour cycle.
The pineal gland secretes less melatonin when exposed to bright light; therefore, the level of this chemical is lowest during the daytime hours of wakefulness.
Multiple neurotransmitters are thought to play a role in sleep. These include serotonin from the dorsal raphe nucleus, norepinephrine contained in neurons with cell bodies in the locus ceruleus, and acetylcholine from the pontine reticular formation. Dopamine, on the other hand, is associated with wakefulness.
Abnormalities in the delicate balance of all of these chemical messenger systems may disrupt a variety of physiologic, biologic, behavioral, and EEG parameters responsible for REM (ie, active) sleep and NREM (slow-wave) sleep.
Frequency:
In the US: Approximately one third of all Americans have sleep disorders at some point in their lives. Approximately 20-40% of adults report difficulty sleeping at some point each year. Approximately 17% consider the problem to be serious. Sleep disorders are a common reason for patient visits throughout medicine. Approximately one third of adults have insufficient sleep syndrome. Twenty percent of adults report chronic insomnia.
Mortality/Morbidity:
Chronic insomnia is associated with an increased risk of depression, anxiety, excess disability, reduced quality of life, and increased use of health care resources. Insufficient sleep can result in industrial and motor vehicle accidents, somatic complaints, cognitive dysfunction, depression, and decrements in daytime work performance owing to fatigue or sleepiness.
Sex:
Primary insomnia is more common in women, with a female-to-male ratio of 3:2. Hormonal variations during the menstrual cycle or during menopause may cause disruptions in sleep.
Obstructive sleep apnea is more common in men (4%) than in women (2.5%).
Age:
Increasing age predisposes to sleep disorders (5% in persons aged 30-50 y and 30% in those aged 50 y or older). Elderly people experience a decrease in total sleep time, with more frequent awakenings during the night. People who are elderly have a higher incidence of general medical conditions and are more likely to be taking medications that cause sleep disruption.
CLINICAL Section 3 of 10
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History:
Insomnia may present as decreased sleep efficiency or decreased total hours of sleep, with some associated complaint of decreased productivity or well-being. Sleep quality is more important than the total number of hours slept because sleep requirements vary from person to person. Compare the total number of hours slept with each individual's lifelong normal night sleep time.
Initial insomnia is characterized by difficulty falling asleep, with increased sleep latency (time between going to bed and falling asleep). Initial insomnia frequently is related to anxiety disorders.
Middle insomnia refers to difficulty maintaining sleep. Decreased sleep efficiency is the problem, with fragmented unrestful sleep and frequent waking during the night. Middle insomnia may be associated with medical illness, pain syndromes, or depression.
In terminal insomnia, also referred to as early morning wakening, patients consistently wake up earlier than needed. This symptom frequently is associated with major depression.
Alterations of the sleep-wake cycle may be a sign of circadian rhythm disturbances, such as those caused by jet lag and shift work.
Hypersomnia, or excessive daytime sleepiness, often is attributable to ongoing sleep deprivation or poor quality sleep for reasons ranging from sleep apnea to substance abuse or medical problems.
In delayed sleep phase syndrome, the patient is unable to fall asleep until very early morning. As time progresses, the onset of sleep becomes progressively delayed.
Sleepwalking, also called somnambulism, refers to episodes of complex behaviors during NREM sleep (stages 3 and 4) of which the patient is amnestic afterward.
Nightmares are repeated awakenings from sleep caused by vivid and distressing recall of dreams. Nightmares usually occur during the second half of the sleep period. Upon wakening from the dream, the person rapidly reorients to time and place.
Night terrors are recurrent episodes of abrupt awakening from sleep characterized by a panicky scream, with intense fear and autonomic arousal. The individual usually has no recall of the details of the event and is unresponsive during the episode. These episodes occur during the first third of the night, during stages 3 and 4 of NREM sleep.
The bed partner of patients who snore may provide a history of snoring. Such a history has important implications because it may help identify obstructive sleep apnea.
Causes:
The major causes of insomnia may be divided into medical conditions, psychological conditions, and environmental problems.
Medical conditions
Cardiac conditions include ischemia and congestive heart failure.
Neurologic conditions include stroke, degenerative conditions, dementia, peripheral nerve damage, myoclonic jerks, restless legs syndrome, hypnic jerk, and central sleep apnea.
Endocrine conditions affecting sleep are related to hyperthyroidism, menopause, the menstrual cycle, pregnancy, and hypogonadism in elderly men.
Pulmonary conditions include chronic obstructive pulmonary disease, asthma, central alveolar hypoventilation (the Ondine curse), and obstructive sleep apnea syndrome (associated with snoring).
Gastrointestinal conditions include gastroesophageal reflux disease.
Hematological conditions include paroxysmal nocturnal hemoglobinuria, which is a rare, acquired, hemolytic anemia associated with brownish-red morning urine. Substances that may result in insomnia include stimulants, opioids, caffeine, and alcohol, or, withdrawal from any of these also may cause insomnia. Medications implicated in insomnia include decongestants, corticosteroids, and bronchodilators.
Other conditions include fever, pain, and infection.
Psychiatric conditions: Bear in mind that the major psychiatric conditions now are known to have a biological basis and constitute a subset of medical conditions.
Depression may cause alterations in REM sleep. As many as 40% of people with depression have insomnia.
Anxiety disorders predispose to insomnia. The most common of these are generalized anxiety disorder, panic disorder, and anxiety disorders not otherwise specified.
Thought disorders and misperception of sleep state are other potential states that cause insomnia.
Psychotropic medications such as antidepressants may interfere with normal REM sleep patterns.
Rebound insomnia from benzodiazepines or other hypnotic agents is common.
Environmental problems
Stressful or life-threatening events (eg, bereavement) may cause insomnia.
Shift work may disturb the sleep cycle, as might jet lag or changes in altitude.
Sleep deprivation may occur as a result of environmental noise or frequent intrusions (such as in an intensive care unit setting).
DIFFERENTIALS Section 4 of 10
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Alcoholism
Anxiety Disorders
Bipolar Affective Disorder
Breathing-Related Sleep Disorder
Chronic Obstructive Pulmonary Disease
Depression
Emphysema
Hyperthyroidism
Hypoparathyroidism
Opioid Abuse
Posttraumatic Stress Disorder
Sleep Apnea
Related Articles
Alcoholism
Anxiety Disorders
Bipolar Affective Disorder
Breathing-Related Sleep Disorder
Chronic Obstructive Pulmonary Disease
Depression
Emphysema
Hyperthyroidism
Hypoparathyroidism
Opioid Abuse
Posttraumatic Stress Disorder
Sleep Apnea
WORK UP Section 5 of 10
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Lab Studies:
Hemoglobin and hematocrit
Thyroid function tests
Drug and alcohol toxicology screening
Imaging Studies:
Although no imaging studies are indicated directly for the Work up of insomnia, underlying medical conditions require appropriate investigation using suitable studies.
Other Tests:
Oximetry may be performed during sleep to examine blood oxygen levels for clinically important desaturations.
Procedures:
Subjective measures of sleep are obtained by means of a sleep journal. A sleep journal kept for approximately 2 weeks may help determine the extent of the sleep disturbance. Patients should record the total hours slept per night, frequency of nighttime awakenings, and level of restfulness provided after sleep.
Further objective history might be available if patients have a sleep partner who keeps a 2-week journal or provides history.
Objective measures of sleep may be obtained using EEG monitoring or polysomnography. The criterion standard is polysomnography, which includes EEG, electrooculogram, and chin electromyogram. This study can help the physician discriminate between REM and NREM sleep.
Polysomnogram may be useful in determining the etiology of the sleep disturbance. These studies may be helpful in determining sleep and wakefulness in the intensive care unit or in the sleep laboratory.
TREATMENT Section 6 of 10
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Medical Care:
Evaluate patients for other primary sleep disorders (eg, sleep apnea) and for underlying medical, psychiatric, and substance abuse disorders, and institute appropriate treatment. Sleep hygiene and behavioral strategies are used in combination with medication to treat insomnia, particularly primary insomnia.
Education about good sleep practices is essential for effective treatment of insomnia.
Use the bed for sleep and sex only (no television watching or reading in bed).
Do not watch the clock while in bed. Practice relaxation techniques before bedtime. Avoid stimulating activities during the 3 hours before bedtime, such as heavy exercise, tense or thrilling reading or television, or arguments.
Maintain a regular schedule for bedtime and wakening; avoid naps. Early to rise and early to bed is the most effective schedule. A "night owl" schedule is poor sleep hygiene.
Avoid struggling to fall asleep in bed. Instead, get up and spend quiet time out of bed until sleep comes.
Light-phase shift therapy is useful for sleep disturbances associated with circadian rhythm abnormalities. Patients may be exposed to bright light, either from a light box or natural sunlight, to help normalize the sleep schedule.
Surgical Care:
Surgical referral may be indicated to correct some underlying medical conditions that cause insomnia, such as for palate surgery in some cases of sleep apnea.
Consultations:
Consultation can help evaluate patients for medical (including psychiatric) causes of insomnia. The evaluation team optimally should include a psychiatrist, neurologist, pulmonologist, sleep medicine specialist, and dietitian.
Diet:
No special diet is needed to treat insomnia, but large meals and spicy foods should be avoided in the 3 hours before bedtime. Patients should avoid sleep-disturbing substances such as alcohol, nicotine, and caffeine. Alcohol creates the illusion of good sleep, but sleep architecture is affected adversely. Nicotine and caffeine are stimulating and should be avoided in the second half of the day, from late afternoon on. Consumption of tryptophan-containing foods may help induce sleep. The classic example is warm milk.
Activity:
Strenuous exercise during the day may promote better sleep, but this same exercise during the 3 hours before bedtime can cause initial insomnia. Stimulating activities should be avoided 3 hours before bedtime. Examples include tense movies, exciting novels, thrilling television shows, arguments, and vigorous physical exercise other than coitus.
MEDICATION Section 7 of 10
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Many agents are useful in treating insomnia. Short-term drug therapy is preferred to restore a normal sleep pattern. Generally, hypnotic drugs are approved for 2 weeks or less of continuous use. In chronic insomnia, longer courses may be indicated, which require long-term monitoring to ensure ongoing appropriate use of the medication.
Barbiturates and chloral hydrate seldom are used now because of safety concerns related to their undesirably low therapeutic indexes.
Drugs that block the histamine type 1 receptor are used primarily in over-the-counter preparations, are inexpensive, and are helpful to some patients. However, in view of the anticholinergic properties of these agents, caution should be exercised in their use with older patients and with those who have disorders such as prostatic hypertrophy, cognitive disorders, and constipation.
Zolpidem and zaleplon are the newest and, arguably, the safest agents specifically designed for short-term hypnotic use.
Drug Category:
Benzodiazepines -- Benzodiazepine receptor agonists are the mainstay in treatment of insomnia. Flurazepam, temazepam, quazepam, estazolam, and triazolam are the benzodiazepines that are approved by the US Food and Drug Administration as hypnotics.
These drugs bind to a special benzodiazepine site on the GABA receptor complex, enhancing activity of this neurotransmitter. All have variable half-lives and different metabolites that affect their onset and duration of action. This class of drugs suppresses REM sleep and reduces stages 3 and 4 sleep while increasing stage 2 sleep. The drug described here, temazepam, is only one example of this class of medications. A more detailed discussion of the other agents in this class can be found elsewhere in the text.
Drug Name
Temazepam (Restoril) -- Its intermediate rate of absorption and duration of action make this drug useful for treating initial and middle insomnia. Has no active metabolites, which reduces cognitive impairment and grogginess the following day.
Adult Dose 15-30 mg PO qhs
Pediatric Dose Not established
Contraindications Documented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse; severe uncontrolled pain
Interactions Cimetidine, disulfiram, isoniazid, and estrogen increase plasma levels of benzodiazepines; benzodiazepines may increase levels of dioxin and phenytoin; other sedating drugs have additive effects with benzodiazepines
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Caution in chronic respiratory or hepatic disease and in elderly patients; avoid in individuals with history of substance abuse; effect of respiratory compromise more pronounced when ingested with alcohol; may have associated tolerance, dependence, daytime sedation/hangover effect, and withdrawal syndromes; long-term use may result in cognitive dysfunction and rebound insomnia when discontinued
Drug Category:
Imidazopyridine -- Zolpidem is the sole member of this class of medications. It binds at a benzodiazepine receptor subtype (omega I). Found more in CNS more than in peripheral nervous system, which helps to account for hypnotic effect with no significant muscle-relaxant properties. Unlike benzodiazepines, normal sleep architecture not suppressed.
Drug Name
Zolpidem (Ambien) -- Rapidly absorbed, with fast onset (2.5-3 h) of action, which makes this a good drug for sleep induction.
Adult Dose 5-20 mg PO qhs
Pediatric Dose Not established
Contraindications Documented hypersensitivity; lactation
Interactions Increases toxicity of alcohol and CNS depressants
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Decrease dose to 5 mg in patients who are elderly or debilitated because of greater possibility of impaired motor and/or cognitive difficulties
Caution with pulmonary dysfunction
Drug Category:
Pyrazolopyrimidine -- Zaleplon is the sole agent in this class of nonbenzodiazepine hypnotics.
Drug Name
Zaleplon (Sonata) -- Not structurally related to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. Interacts with GABA-benzodiazepine receptor complex, causing effects in sedation, anxiolytic activity, and muscle relaxation. Should be taken immediately before bedtime.
Shorter onset of action means peak serum concentrations achieved within 1 h of administration. This may account for lower incidence of daytime grogginess and less withdrawal rebound insomnia.
Adult Dose 10 mg PO qhs; dose may be halved or doubled depending on patient weight and/or response to drug
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Interactions May interact with drugs metabolized by aldehyde oxidase and CYP3A4, including diphenhydramine and cimetidine; cimetidine significantly increases levels of zaleplon
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Taking drug while still awake and active may cause hallucination, short-term memory impairment, impaired coordination, light-headedness, and dizziness; failure of insomnia to remit after 7-10 d of treatment may indicate need for evaluation for primary psychiatric or medical illness; limit treatment to 7-10 d and reevaluate patient if drug to be taken for >2-3 wk (do not prescribe zaleplon in quantities exceeding 1-mo supply); in hepatic function impairment, reduce dose to 5 mg PO hs; caution in patients exhibiting signs or symptoms of depression
Drug Category:
Antidepressants -- Although no antidepressants are approved specifically for use in sleep disorders, a cyclic antidepressant, trazodone (Desyrel), is used routinely for this purpose.
Drug Name
Trazodone (Desyrel) -- Mechanism of action not fully understood. Thought to selectively inhibit serotonin uptake by brain synaptosomes and potentiate behavioral changes induced by serotonin precursor, 5-HT. Major adverse effect is sedation.
Adult Dose Starting dose: 50 mg PO qhs
Usual dose range for insomnia: 50-100 mg, but up to 300 mg may be needed; not to exceed 400 mg
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Interactions May enhance response to alcohol, barbiturates, and other CNS depressants; may decrease hypoprothrombinemic effects of warfarin; dioxin and phenytoin serum levels may increase with concomitant trazodone
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Hypotension has occurred, including orthostatic hypotension and syncope; may produce drowsiness, dizziness, or blurred vision; observe caution while driving or performing other tasks requiring alertness, coordination, or dexterity; priapism reported in patients taking trazodone; patients with prolonged or inappropriate penile erection should immediately seek emergency medical treatment and discontinue drug
FOLLOW-UP Section 8 of 10
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Further Inpatient Care:
This is rarely, if ever, required for treatment of insomnia. Only a severe underlying medical, psychiatric, or substance abuse disorder would warrant inpatient care.
Further Outpatient Care:
Given the complexity of diagnosing sleep disorders, with multiple possible medical etiologies, regular appropriate follow-up care is necessary until final diagnosis and successful treatment of the condition. Involvement of one or several medical specialists for care and consultations, if needed, can be coordinated by the patient's internist or other personal physician or by the medical sleep specialist.
In/Out Patient Meds:
Once appropriate medication, if needed, is in use successfully, regular follow-up should be provided, even if infrequently.
Deterrence/Prevention:
In addition to specific treatment for diagnosed sleep disorders, good sleep hygiene should be taught to every patient (and this information should be publicly available). Just as with dental hygiene, appropriate sleep habits should be cultivated by all individuals all the time.
See Medical Care for more information.
Complications:
Mood and anxiety disorders may develop from untreated sleep disturbances, and current medical literature supports the theory that these brain-based mental status changes are risk factors for morbidity and mortality from a host of medical conditions (eg, cardiovascular disease).
Prognosis:
The prognosis varies widely depending on the etiology of the insomnia or other sleep disorder. For example, insomnia due to obstructive sleep apnea resolves with successful treatment of the apnea, while insomnia due to refractory major depression is itself refractory until a successful treatment can be found for the depression.
Patient Education:
All individuals should be educated about and encouraged to practice good sleep hygiene, as outlined in Medical Care.
Use the bed for sleep and sex only (no television watching or reading in bed).
MISCELLANEOUS Section 9 of 10
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Medical/Legal Pitfalls:
Patients should be warned to not drive or operate machinery while taking sedative-hypnotic medications. Document these admonitions clearly in the medical record. Caution is advised in the treatment of patients who are elderly and others who may be at increased risk for falls.
BIBLIOGRAPHY Section 10 of 10
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American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: APA Press; 1994.
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Ford DE, Kamerow DB: Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA 1989 Sep 15; 262(11): 1479-84[Medline].
Gillin JC, Byerley WF: Drug therapy: The diagnosis and management of insomnia. N Engl J Med 1990 Jan 25; 322(4): 239-48[Medline].
Hauri PJ, Hayes B, Sateia M: Effectiveness of a sleep disorders center: a 9-month follow-up. Am J Psychiatry 1982 May; 139(5): 663-6[Medline].
Kaplan HI, Sadock BJ, Grebb JA: Normal sleep and sleep disorders. In: Kaplan and Sadock's Synopsis of Psychiatry. 7th ed. Baltimore, Md: Williams & Wilkins; 1994: 699-716.
Loewy DH, Black JE: Effective management of transient and chronic insomnia. In: CNS News. New York, NY: McMahon Publishing Group; 2000 Feb: 19-22[Full Text].
Schwab RJ: Disturbances of sleep in the intensive care unit. Crit Care Clin 1994 Oct; 10(4): 681-94[Medline].
Zammit GK, Weiner J, Damato N: Quality of life in people with insomnia. Sleep 1999 May 1; 22 Suppl 2: S379-85[Medline].
NOTE:
Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER
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